Abstract
Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake of dopamine and the anyA9 genotype of this gene is associated with higher striatal dopamine signaling. Expanding these two lines of prior research, we investigated potential interactive effects between aging and individual variations in the DAT1 gene on the modular organization of brain acvitiy during rest. The graph-theoretic metrics of modularity, betweenness centrality and participation coefficient were assessed in 41 younger (age 20–30 years) and 37 older (age 60–75 years) adults. Age differences were only observed in the participation coefficient in carriers of the anyA9 genotype of the DAT1 gene and this effect was most prominently observed in the default mode network. Furthermore, we found that individual differences in the values of the participation coefficient correlated with individual differences in fluid intelligence and a measure of executive control in the anyA9 carriers. The correlation between participation coefficient and fluid intelligence was mainly shared with age-related differences, whereas the correlation with executive control was independent of age. These findings suggest that DAT1 genotype moderates age differences in the functional integration of brain networks as well as the relation between network characteristics and cognitive abilities.
Highlights
During alert but task-free states, the brain’s sensorimotor and higher cognitive systems display organized temporal correlations between spontaneous fluctuations of brain activity in different brain regions
Functional magnetic resonance imaging research on the organized patterns of spontaneous brain activity suggests that resting-state functional connectivity is a promising avenue for investigating the dynamics of coherent brain activity patterns that are organized into distinct systems or networks
We found age by genotype interaction effects in resting-state functional magnetic resonance imaging (fMRI) networks that indicate a lower degree of intermodular communication in older adults compared to younger adults who are anyA9 allele carriers of the dopamine transporter gene DAT1, while this effect was absent in A10 homozygotes
Summary
During alert but task-free states, the brain’s sensorimotor and higher cognitive systems display organized temporal correlations between spontaneous fluctuations of brain activity in different brain regions. A range of previous studies have investigated the effects of aging on brain functional connectivity by measuring age differences within networks using seed-based or ICA analyses. The most consistent finding is the observation of reduced intranetwork functional connectivity among regions in the default mode network (DMN) in older compared to younger adults (e.g., [11]; see [7], [12] for overviews). In other cross-sectional studies of internetwork connectivity between the dorsal attentional network, DMN, and the frontoparietal control network has been found to be increased in older compared to younger adults (e.g., [15], [16], [17]), suggesting attenuated system segregation in old age [18]. Unlike the evidence for aging-related decrease in intranetwork rsFC, findings about effects of age on internetwork rsFC are less consistent
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